Novel pthalazinyl derivatives: Synthesis, antimycobacterial activities, and inhibition of Mycobacterium tuberculosis isocitrate lyase enzyme

Medicinal Chemistry

Volumn 5, Issue 5, 2009, Pages 422-433

  Sriram, D ^a   Yogeeswari, P ^a   Senthilkumar, P ^a   Dewakar, S ^a   Rohit, N ^a   Debjani, B ^a   Bhat, Pritesh ^a   Veugopal, B ^a   Pavan, V V S ^a   Thimmappa, H M ^a  

^a BIRLA INSTITUTE OF TECHNOLOGY AND SCIENCE   (India)

Author keywords

Antimycobacterial; Isocitrate lyase; Mycobacterium tuberculosis; Phthalazine

Indexed keywords

2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' (1 PHENYLETHYLIDENE)ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' (DIPHENYLMETHYLENE)ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' (PHENYLMETHYLIDENE)ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [(2 HYDROXYPHENYL)METHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [(2 METHYLPHENYL)METHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [(2 NITROPHENYL)METHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [(2 TRIFLUOROMETHYLPHENYL)METHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [(2,6 DICHLOROPHENYL)METHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [(3 BROMOPHENYL)METHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [(3 FLUOROPHENYL)METHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [(3 NITROPHENYL)METHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [(4 BENZYLOXYPHENYL)METHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [(4 BROMOPHENYL)(PHENYL)METHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [(4 BROMOPHENYL)METHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [(4 DIMETHYLAMINOPHENYL)METHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [(4 FLUOROPHENYL)METHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [(4 HYDROXY 3 METHOXYPHENYL)METHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [(4 METHYLPHENYL)METHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [(4 NITROPHENYL)METHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [(5 NITRO 2 FURYL)METHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [1 (2 HYDROXYPHENYL)ETHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [1 (4 BROMOPHENYL)ETHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [1 (4 FLUOROPHENYL)ETHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [1 (4 HYDROXYPHENYL)ETHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL] N' [1 (4 METHYLYL)ETHYLIDENE]ACETOHYDRAZIDE; 2 [3 (4 BROMO 2 FLUOROBENZYL) 4 OXO 3,4 DIHYDRO 1 PTHALAZINYL]ACETIC ACID HYDRAZONE DERIVATIVE; ISOCITRATE LYASE; ISONIAZID; TUBERCULOSTATIC AGENT; UNCLASSIFIED DRUG; UNINDEXED DRUG; ANTIINFECTIVE AGENT; ENZYME INHIBITOR; PHTHALAZINE DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBACTERIAL ACTIVITY; ARTICLE; BACTERIUM CULTURE; CONTROLLED STUDY; CYTOTOXICITY; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; FEMALE; IN VITRO STUDY; IN VIVO STUDY; MINIMUM INHIBITORY CONCENTRATION; MOUSE; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PRIORITY JOURNAL; TUBERCULOSIS; VERO CELL; ANIMAL; CERCOPITHECUS; CHEMISTRY; DRUG ANTAGONISM; DRUG EFFECT; ENZYMOLOGY; HUMAN; MICROBIOLOGICAL EXAMINATION; SYNTHESIS;

ANIMALS; ANTI-BACTERIAL AGENTS; CERCOPITHECUS AETHIOPS; ENZYME INHIBITORS; FEMALE; HUMANS; ISOCITRATE LYASE; MICE; MICROBIAL SENSITIVITY TESTS; MYCOBACTERIUM TUBERCULOSIS; PHTHALAZINES; VERO CELLS;

EID: 70349150584     PISSN: 15734064     EISSN: None     Source Type: Journal    
DOI: 10.2174/157340609789117886     Document Type: Article

References (45)

1. World Health Organization. Global TB Control Report, 2008.
2. Coninx, R. Tuberculosis in complex emergencies. Bull. World Health Organ., 2007, 85, 637.
3. Del Olmo, E.; Barboza, B.; Ybarra, M.I.; Lopez-Perez, J.L.; Carron, R.; Sevilla, M.A.; Boselli, C.; San Feliciano, A. Vasorelaxant activity of phthalazinones and related compounds. Bioorg. Med. Chem. Lett., 2006, 16, 2786.
4. Madhavan, G.R.; Chakrabarti, R.; Kumar, S.K.; Misra, P.; Mamidi, R.N.; Balraju, V.; Kasiram, K.; Babu, R.K.; Suresh, J.; Lohray, B.B.; Lohrayb, V.B.; Iqbal, J.; Rajagopalan, R. Novel phthalazinone and benzoxazinone containing thiazolidinediones as antidiabetic and hypolipidemic agents. Eur. J. Med. Chem., 2001, 36, 627.
5. Bedoya, L.M.; del Olmo, E.; Sancho, R.; Barboza, B.; Beltran, M.; Garcia-Cadenas, A.E.; Sanchez-Palomino, S.; Lopez-Perez, J.L.; Munoz, E.; Feliciano, A.S.; Alcamia, J. Anti-HIV activity of stilbene-related heterocyclic compounds. Bioorg. Med. Chem. Lett., 2006, 16, 4075.
6. Cockcroft, X.L.; Dillon, K.J.; Dixon, L.; Drzewiecki, J.; Kerrigan, F.; Loh, V.M.; Martin, N.M. Phthalazinones 2: Optimisation and synthesis of novel potent inhibitors of poly(ADP-ribose)polymerase. Bioorg. Med. Chem. Lett., 2006, 16, 1040.
7. Mey, V.M.; Bommele, K.M.; Boss, H.; Hatzelmann, A.; Slingerland, V.M.; Sterk, G.J.; Timmerman, H. Synthesis and structure-activity relationships of cis-tetrahydrophthalazinone/pyridazinone hybrids: a novel series of potent dual PDE3/PDE4 inhibitory agents. J. Med. Chem., 2003, 46, 2008.
8. Yamaguchi, M.; Koga, T.; Kamei, K.; Akima, M.; Maruyama, N.; Kuroki, T.; Hamana, M.; Ohi, N. Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. IV. 2-[2-(1-Imidazolyl)ethyl]-4-(3-pyridyl)-1(2H)-phthalazinones. Chem. Pharm. Bull., 1994, 42, 1850.
9. Kumar, R.R.; Perumal, S.; Senthilkumar, P.; Yogeeswari, P.; Sriram, D. Discovery of antimycobacterial spiro-piperidin-4-ones: an atom economic, stereoselective synthesis, and biological intervention. J. Med. Chem., 2008, 51, 5731.
10. Dinakaran, M.; Senthilkumar, P.; Yogeeswari, P.; China, A.; Nagaraja, V.; Sriram, D. Synthesis, antimycobacterial activities and phototoxic evaluation of 5H-thiazolo[3,2-a]quinoline-4-carboxylic acid derivatives. Med. Chem., 2008, 4, 482.
11. Dinakaran, M.; Senthilkumar, P.; Yogeeswari, P.; China, A.; Nagaraja, V.; Sriram, D. Novel ofloxacin derivatives: synthesis, antimycobacterial and toxicological evaluation. Bioorg. Med. Chem. Lett., 2008, 18, 1229.
12. Senthilkumar, P.; Dinakaran, M.; Banerjee, D.; Devakaram, R.V.; Yogeeswari, P.; China, A.; Nagaraja, V.; Sriram, D. Synthesis and antimycobacterial evaluation of newer 1-cyclopropyl-1,4-dihydro-6-fluoro-7-(substituted secondary amino)-8-methoxy-5-(sub)-4-oxoquinoline-3-carboxylic acids. Bioorg. Med. Chem., 2008, 16, 2558.
13. Dinakaran, M.; Senthilkumar, P.; Yogeeswari, P.; China, A.; Nagaraja, V.; Sriram, D. Antimycobacterial activities of novel 2-(sub)-3-fluoro/ nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid. Bioorg Med Chem., 2008, 16, 3408.
14. Dinakaran, M.; Senthilkumar, P.; Yogeeswari, P.; China, A.; Nagaraja, V.; Sriram, D. Int. Antimycobacterial and phototoxic evaluation of novel 6-fluoro/nitro-4-oxo-7-(sub)-4H-[1,3]thiazeto [3,2-a]quinoline-3-carboxylic acid. J. Antimicrob. Agents, 2008, 31, 337.
15. Sriram, D.; Senthilkumar, P.; Dinakaran, M.; Yogeeswari, P.; China, A.; Nagaraja, V. Antimycobacterial activities of novel 1-(cyclopropyl/ tert-butyl/4-fluorophenyl)-1,4-dihydro- 6-nitro-4-oxo-7-(substituted secondary amino)-1,8-naphthyridine-3-carboxylic acid. J. Med. Chem., 2007, 50, 6232.
16. Sriram, D.; Yogeeswari, P.; Dinakaran, M.; Thirumurugan, R. Antimycobacterial activity of novel 1-(5-cyclobutyl-1,3-oxazol-2-yl)-3-(sub)phenyl/pyridylthiourea endowed with high activity toward multi-drug resistant tuberculosis. J. Antimicrob. Chemother., 2007, 59, 1194.
17. Kumar, R.R.; Perumal, S.; Senthilkumar, P.; Yogeeswari, P.; Sriram, D. An atom efficient, solvent-free, green synthesis and antimycobacterial evaluation of 2-amino-6-methyl-4-aryl-8-[(E)-arylmethylidene]-5,6,7,8- tetrahydro-4H-pyrano[3,2-c]pyridine-3-carbonitriles. Bioorg. Med. Chem. Lett., 2007, 17, 6459.
18. Sriram, D.; Yogeeswari, P.; Thirumurugan, R.; Kumar, P.R. Discovery of newer antitubercular oxazolyl thiosemicarbazones. J. Med. Chem., 2006, 49, 3448.
19. Vedejs, E.; Marth, C.F. Synthetic enantiopure aziridinomitosenes: preparation, reactivity, and DNA alkylation studies. J. Am. Chem. Soc., 1988, 110, 3948.
20. Kangani, C.O.; Master, H.E. Preparation of 1-aminoanthraquinone-2-carbohydrazide, 1.3.4-oxadiazoles, pyrazoles, pyrimidines and phthalazines. Ind. J. Chem., 1998, 37, 778.
21. National Committee for Clinical Laboratory Standards. Antimycobacterial susceptibility testing for Mycobacterium tuberculosis. Proposed standard M24-T. National Committee for Clinical Laboratory Standards: Villanova, Pa., 1995.
22. Katoch, V.M. Infections due to non-tuberculous mycobacteria (NTM). Ind. J. Med. Res., 2004, 120, 290.
23. Schreiber, J.; Burkhardt, U.; Rusch-Gerdes, S.; Amthor, M.; Richter, E.; Zugehor, M.; Rosahl, W.; Ernst, M. Non-tubercular mycobacterial infection of the lungs due to Mycobacterium smegmatis. Pneumologie, 2001, 55, 238.
24. Geiss, H.K.; Feldhues, R.; Niemann, S.; Nolte, O.; Rieker, R. Landouzy septicemia (sepsis tuberculosa acutissima) due to Mycobacterium microti in an immunocompetent man. Infection, 2005, 33, 393.
25. Hachem, R.; Raad, I.; Rolston, K.V.; Whimbey, E.; Katz, R.; Tarrand, J.; Libshitz, H. Cutaneous and pulmonary infections caused by Mycobacterium vaccae. Clin. Infect. Dis., 1996, 23, 173.
26. Spiegl, P.V.; Feiner, C.M. Mycobacterium phlei infection of the foot: a case report. Foot Ankle Int., 1994, 15, 680.
27. O' Brien, R.J.; Geiter, L.J.; Snider, D.E. The epidemiology of nontuberculous mycobacteria disease in the United States; results from a national survey. Am. Rev. Respir. Dis., 1987, 135, 1007.
28. Tabatabaei, N.; Stout, J.; Goldschmidt-Clermont, P.; Murdoch, D. Central nervous system infection and cutaneous lymphadenitis due to Mycobacterium kansasii in an immunocompetent patient. Infection, 2007, 35, 291.
29. Xie, Z.; Siddiqi, N.; Rubin, E.J. Differential antibiotic susceptibilities of starved Mycobacterium tuberculosis isolates. Antimicrob. Agents Chemother., 2005, 49, 4778.
30. Wayne, L.G.; Sohaskey, C.D. Non-replicating persistence of Mycobacterium tuberculosis. Annu. Rev. Microbiol., 2001, 55, 139.
31. Betts, J.C. Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol. Microbiol., 2002, 43, 717.
32. Hu, Y.; Coates, A.R.M.; Mitchison, D.A. Sterilizing activities of fluoroquinolones against rifampin-tolerant populations of Mycobacterium tuberculosis. Antimicrob. Agents Chemother., 2003, 47, 653.
33. Betts, J.C.; Lukey, P.T.; Robb, L.C.; Mc Adam, R.A.; Duncan, K. Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol. Microbiol., 2002, 43, 717.
34. Mc Dermott, W. Microbial persistence. Yale J. Biol. Med., 1958, 30, 257.
35. Zhang, Y. Persistent and dormant tubercle bacilli and latent tuberculosis. Front. Biosci., 2004, 9, 1136.
36. O'Brien, R.J.; Nunn, P.P. The need for new drugs against tuberculosis. Obstacles, opportunities, and next steps. Am. J. Respir. Crit. Care Med., 2001, 163, 1055.
37. Zhang, Y. The magic bullets and tuberculosis drug targets. Annu. Rev.Pharmacol. Toxicol., 2005, 45, 529.
38. McKinney, J.D.; Bentrup, K.H.; Muñoz-Elías, E.J.; Miczak, A.; Chen, B.; Chan, W.T.; Swenson, D.; Sacchettini, J.C.; Jacobs, W.R.; Russell, D.G. Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature, 2000, 406, 735.
39. Glickman, M.S. A novel mycolic acid cyclopropane synthetase is required for cording, persistence, and virulence of Mycobacterium tuberculosis. Mol. Cell, 2000, 5, 717.
40. Dahl, J.L. The role of RelMtb-mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice. Proc. Natl. Acad. Sci. USA, 2003, 100, 10026.
41. Park, H.D. Rv3133c/dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis. Mol. Microbiol., 2003, 48, 833.
42. Bentrup, K.H.Z.; Miczak, A.; Swenson, D.L.; Russell, D.G. Characterization of activity and expression of isocitrate lyase in Mycobacterium avium and Mycobacterium tuberculosis. J. Bacteriol., 1999, 181, 7161.
43. Bai, B.; Xie, J.P.; Yan, J.F.; Wang, H.; Hu, C. A high throughput screening approach to identify isocitrate lyase inhibitors from traditional chinese medicine sources. Drug Dev. Res., 2006, 67, 818.
44. Gundersen, L.L.; Nissen-Meyer, J.; Spilsberg, B. Synthesis and antimycobacterial activity of 6-arylpurines: The requirements for the N-9 substituent in active antimycobacterial purines. J. Med. Chem., 2002, 45, 1383.
45. Sriram, D.; Yogeeswari, P.; Basha, S.J.; Radha, D.R.; Nagaraja, V. Synthesis and antimycobacterial evaluation of various 7- substituted ciprofloxacin derivatives. Bioorg. Med. Chem., 2005, 13, 5774.